One of the main causes of senile cataract may be a derangement in the defense system of the lens against oxidative damage. Superoxide dismutase, catalase, (the catalatic and the peroxidatic activities), glutathione peroxidase, glutathione reductase and glucose-6-P dehydrogenase are the key enzymes for reducing the oxidants such as superoxide anions, hydrogen peroxide and lipid hydroperoxides. The physiological significance of each of these enzymes will be studied in selenium deficient-acatalasemic mice. Severe selenium deficiency will be produced in acatalasemic mice by feeding selenium deficient diet for three to four generations. This will produce severe glutathione peroxidase deficiency. In addition, the role of glutathione in the maintenance of lens clarity and in the detoxification of xenobiotics via mercapturic acid pathway will be studied. All the glutathione of the lens will be conjugated with substrates of glutathione S-transferase, and the effect of oxidative challenge by superoxide anion and/or hydrogen peroxide will be studied. These studies will help in the understanding of the defense system of the lens against oxidative damage and the role of glutathione in the lens. The other aim of the project is to study the mechanisms of formation of diabetic and galactasemic cataract. The effect of aldose reductase inhibitors, which delay or prevent sugar cataracts on the activity of aldose and aldehyde reductases purified to homogeneity from human lens and other tissues will be studied. A study of the structural, kinetic and immunological properties of the enzymes will establish the biochemical and genetic interrelationship among the aldehyde and aldose reductases present in various human tissues. We have proposed an alternative pathway of glucose metabolism via sorbitol-6-P pathway. The kinetic properties of all the enzymes involved in the pathway along with the characterization of the reaction products will be performed. Furthermore, the contents of phosphorylated sorbitol will be determined in the lens of diabetic and galactosemic animals and in diabetic subjects. The phosphorylated sorbitol may be more impermeable than sorbitol. These studies will significantly help in the understanding of the mechanism(s) of sugar cataract formation.